报告题目: Chromatin Topology Reorganization and Transcription Repression by PML/RARa in Acute Promyeloid Leukemia

报告人：Ping Wang

报告时间：2019年10月15日（周二）10:00

报告地点：逸夫楼C座314会议室

摘要：

Acute promyeloid leukemia (APL) is characterized by the oncogenic fusion protein PML/RARa, a major etiological agent in APL. However, the molecular mechanisms underlying the role of PML/RARa in leukemogenesis remains largely unknown. Here, using an inducible system, we comprehensively analyzed the 3D genome organization in myeloid cells and its reorganization after PML/RARa induction, and performed additional analyses in patient-derived APL cells with native PML/RARa. We discovered that PML/RARa mediates extensive chromatin interactions genome-wide. Globally, it redefines the chromatin topology of the myeloid genome toward a more condensed configuration in APL cells; locally, it intrudes RNAPII-associated interaction domains, interrupts myeloid-specific transcription factors binding at enhancers and super-enhancers, and leads to transcriptional repression of genes critical for myeloid differentiation and maturation. Together, our results provide novel topological insights for the roles of PML/RARa in transforming myeloid cells into leukemia cells, likely a general mechanism for oncogenic fusion proteins in cancers.

报告人简介：

王萍博士2012年10月加入美国杰克逊实验室，从事白血病领域三维转录调控机制研究。在此期间不仅参与长片段ChIA-PET、RICH-PET及All-Seq技术平台的改进，而且参加了多项NIH的合作研究项目。目前担任人类基因组解析计划-ENCODE项目的研究工作。